Selective destruction of the serotonergic fibers of the fornix-fimbria and cingulum bundle increases 5-HT₁ but not 5-HT₂ receptors in rat midbrain

Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [³H]5-HT (5-HT₁ receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the B_max in the midbrain (38%) with no change in the K_D. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT₁ receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [³H]spiroperidol and [³H]ketanserin to the 5-HT₂ receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT₁ receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT₂ binding is not altered, this further supports the hypothesis that 5-HT₁ and 5-HT₂ receptors are distinct populations of receptors.